Li Wu Zheng

Changes in blood perfusion and bone healing induced by nicotine during distraction osteogenesis

Nicotine is the main chemical in cigarettes responsible for the tobaccos pathological effects. The influence of nicotine on bone healing remains controversial. Distraction osteogenesis provides an ideal model to study bone healing and regeneration. The present study aims to evaluate the effects of nicotine on blood perfusion, angiogenesis and bone formation using a rabbit model of mandibular lengthening. Twenty adult New Zealand white rabbits were randomly assigned to the control group and nicotine group. The total nicotine or placebo exposure time for all animals was 7 weeks. After 2- or 4-week of consolidation following osteotomy, 3-day of latency and 11-day of active distraction, the animals were sacrificed and the mandibles were harvested. Blood perfusion and vascularization were evaluated by Laser Doppler monitoring and Collagen IV immunohistochemistry staining respectively. Bone formation was assessed by radiological, histological and immunohistochemical examination. Results showed that nicotine exposure increased microvessel density, whereas inhibited blood flow and bone formation. The expression of bone morphogenetic protein (BMP)-2 in osteoblasts was also decreased. Frequent appearance of cartilage islands suggested ischemia and low oxygen tension in the distraction regenerate. We concluded that nicotine compromises bone regeneration possibly by causing ischemia and directly inhibitory effect on osteoblastic cells. Nicotine exposure enhances angiogenesis but cannot compensate for the adverse effect of vasoconstriction.

Uncoupled Angiogenesis and Osteogenesis in Nicotine-Compromised Bone Healing

Nicotine is the main chemical component responsible for tobacco addiction. This study aimed to evaluate the influence of nicotine on angiogenesis and osteogenesis and the associated expression of angiogenic and osteogenic mediators during bone healing. Forty‐eight adult New Zealand White rabbits were randomly assigned to a nicotine group and a control group. Nicotine pellets (1.5 g, 60‐day time release) or placebo pellets were implanted in the neck subcutaneous tissue. The nicotine or placebo exposure time for all the animals was 7 weeks. Unilateral mandibular distraction osteogenesis was performed. Eight animals in each group were euthanized on day 5, day 11 of active distraction, and week 1 of consolidation, respectively. The mandibular samples were subjected to radiographic, histologic, immunohistochemical, and real‐time reverse‐transcriptase polymerase chain reaction examinations. Nicotine exposure upregulated the expression of hypoxia inducible factor 1α and vascular endothelial growth factor and enhanced angiogenesis but inhibited the expression of bone morphogenetic protein 2 and impaired bone healing. The results indicate that nicotine decouples angiogenesis and osteogenesis in this rabbit model of distraction osteogenesis, and the enhanced angiogenesis cannot compensate for the adverse effects of nicotine on bone healing.

Effect of recombinant human bone morphogenetic protein-2 on mandibular distraction at different rates in an experimental model.

This study evaluates the effect of recombinant human (rh) bone morphogenetic protein (BMP)-2 on mandibular distraction at normal and rapid distraction rates. This study also determines the feasibility of compensating for the increased distraction rate by the addition of rhBMP-2 while maintaining the quality of the distraction regenerate. Twenty-four New Zealand white rabbits were divided into 2 groups, 1 treated at a normal distraction rate (0.9 mm/d) and the other at a rapid distraction rate (2.7 mm/d). At the end of the active distraction period, rhBMP-2 was injected into distraction regenerate, and the contralateral side was used as a control. The distraction regenerates were analyzed by plain radiography, microcomputed tomography, and mechanical testing. The results showed that rhBMP-2 can promote bone formation at both rapid and normal distraction rates. At week 2 and week 4 of consolidation, bone volumes in the BMP-injection sides were significantly higher than in the control sides, but no statistically significant difference was observed between the BMP-injection sides of the rapid and normal distraction groups. At week 8 of consolidation, mechanical testing demonstrated no significant difference of the failure load and stiffness between the BMP-injection and control sides. In conclusion, the study indicates that rhBMP-2 can enhance bone ossification at both normal and rapid distraction rates. The addition of rhBMP-2 can compensate for the rapid distraction rate in mandibular distraction osteogenesis. However, in the long term, the bone quality and stiffness of the distraction regeneration was not influenced by rhBMP-2.

Influence of nicotine on the biological activity of rabbit osteoblasts

OBJECTIVES To assess the influence of nicotine on the proliferation and gene expression of osteogenic and angiogenic mediators of osteoblasts. MATERIAL AND METHODS Rabbit primary osteoblasts were exposed to various concentrations of nicotine (0.001, 0.1 and 10 μmol/l). The cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The gene expression of transforming growth factor (TGF)-β(1), bone morphogenetic protein (BMP)-2, platelet-derived growth factor (PDGF)-AA and vascular endothelial growth factor (VEGF) was evaluated using real-time reverse transcription - polymerase chain reaction. RESULTS The osteoblast proliferation was inhibited by nicotine at the concentration of 0.001-10 μM at 48 and 72 h of culture, but with no significant effect at 24 h. The expression of TGF-β(1), BMP-2, PDGF-AA and VEGF was inhibited by nicotine at the concentrations of 0.1 and 10 μM, but with no significant difference at the low concentration of 0.001 μM. CONCLUSIONS Nicotine suppresses osteoblast proliferation and inhibits the expression of some key osteogenic and angiogenic mediators in the in vitro experimental model. These inhibitory effects of nicotine on the osteoblast activity may reflect, to a certain degree, the overall detrimental effects of tobacco use on the survival rate of dental implants.

Skeletal site-specific response to ovariectomy in a rat model: change in bone density and microarchitecture.

OBJECTIVES Ovariectomized (OVX) rat model has been widely used in osteoporosis-related studies. However, the discrepancies in age and skeletal sites being investigated make it difficult to compare the results from different studies. The purpose of this study was to provide information of systemic skeletal site-specific changes in a stable OVX rat model. MATERIAL AND METHODS Thirty-three 6-month Spraque-Dawley female rats were used. Fifteen rats underwent ovariectomy, and fifteen received sham surgery. Three animals without any surgery were sacrificed at week 0 to serve as baseline. Three animals in the OVX and sham group, respectively, were euthanized at week 2, 4, 12, 24 and 36 post-surgery. Ten bone sites, including parietal bone, interparietal bone, maxilla, mandible, humerus, ulna, femur, tibia, lumber vertebra, and ilium, were subjected to micro-CT. RESULTS Overall, long bones, lumber vertebra, and ilium showed similar trend of bone loss post-OVX, with tibia and femur suffered the most bone loss and spine the least (decreased by 75.0%, 70.4% and 36.6% in bone mineral density BMD at week 36 from base line, respectively). Upon OVX, jaw bones and cranial bones only showed a minor reduction in BMD (decreased by 1~3% from baseline) at week 36. Significant deterioration of trabecular structure was detected in long bones, lumber vertebra, and ilium post-OVX, while jaw bones remained relatively stable. CONCLUSIONS This study for the first time assessed the systemic site-specific bone loss and microarchitecture changes in OVX rat model. It provided valuable information for selecting bone site and observation time in osteoporosis-related study.

Traditional Chinese medicine and oral diseases: today and tomorrow

With a history of over 2000 years, traditional Chinese medicine (TCM) evolves into a unique system of diagnosing and treating illnesses. It is a challenge to convey the fundamentals of this traditional medicine to our Western colleagues because of the differences in language, philosophy and concept of diagnosis and treatment. This review attempts to tackle these barriers by introducing several widely used Chinese medicines for treating oral diseases. China Journals Full-text Database and Pubmed were used as the searching engines. Although many studies have demonstrated that the Chinese medicines are effective in treating oral diseases including recurrent aphthous stomatitis, oral lichen planus, leukoplakia, and Sjögrens syndrome, most of them lacked standard criteria of post-treatment assessment and laboratory evidence. Randomized controlled clinical trials with specific assessment criteria are required to close the gap between TCM and evidenced-based medicine.

Angiogenesis is enhanced by continuous traction in rabbit mandibular distraction osteogenesis

BACKGROUND Distraction osteogenesis is a controlled surgical procedure that initiates a regenerative process and uses mechanical strain to enhance the biological responses of the injured tissues to create new bone. To test the hypothesis that high frequency mechanical traction can enhance the angiogenesis in distraction regenerate, we compared the neo-vessel formation and gene expression of the angiogenic mediators between intermittent and continuous distraction osteogenesis. MATERIAL AND METHODS Eighty adult New Zealand white rabbits were randomly assigned to the continuous and intermittent distraction groups. Unilateral mandibular osteotomy was performed and custom-designed manual-driven or autodriven distractor was bridged over the osteotomy segments. Animals were sacrificed at day-6, day-10, day-14 and day-21 after osteotomy and examined with histology, immunohistochemistry and real-time polymerase chain reaction (PCR). RESULTS Histological examination showed a more advanced bone formation in the continuous distraction group associated with significantly increased micro-vascular density and up-regulated mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). CONCLUSION We concluded that the high frequency traction provides a proper mechanical environment for angiogenesis contributing to the enhanced bone formation likely to be through up-regulation of the angiogenic mediators.

Effect of Recombinant Human Bone Morphogenetic Protein-2 on Mandibular Distraction at Different Rates in a Rabbit Model

This study aims to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on mandibular distraction at routine and rapid distraction rates. Eighteen New Zealand white rabbits were assigned to 2 groups, 1 treated at a routine distraction rate (0.9 mm/d) and the other at a rapid distraction rate (2.7 mm/d). rhBMP-2 was injected into 1 side of the distraction regenerate at the end of the active distraction period; the contralateral side was used as a control. The distraction regenerates were analyzed by plain radiography, microcomputed tomography, and histologic examination. The results showed that rhBMP-2 can promote bone formation at both rapid and routine distraction rates, but no statistically significant difference was observed between the bone morphogenetic protein injection sides of the rapid and routine distraction groups. In conclusion, the study indicates that rhBMP-2 can enhance bone ossification at both routine and rapid distraction rates. The addition of rhBMP-2 seems to be able to compensate for the rapid distraction rate in mandibular distraction osteogenesis. Further longterm follow-up and mechanical strength test for the support of implants or conventional prostheses are necessary.

Long-pulsed Nd: YAG laser treatment in vascular lesions of the oral cavity

Yet no universally accepted treatment protocol for oral hemangiomas and vascular malformations exists. This study determines the long-term clinical outcome after long-pulsed Nd:YAG laser treatment in 121 previously untreated patients (78 females, 43 males; mean age, 19 years) with oral hemangioma or vascular malformations. The end point was 100% vessel clearing after 1 to 3 sessions.The power of the laser was set at 6.5 W per pulse, the pulse widths ranged between 30 and 60 milliseconds. With an optical fiber diameter of 600 &mgr;m, the wavelength was constantly 1064 nm. Dynamic cooling device was set at 10 to 20 and 10 to 15 times before and after pulse, respectively. Whereas 77% of lesions were cleared totally after a single session only, 23% required an overall of 2 to 3 sessions. Tissue sloughing occurred in all patients. The mean follow-up period of 13 months (minimum, 6 months; maximum, 24 months) showed neither functional nor cosmetic shortcomings. Long-pulsed Nd:YAG laser treatment proved to be an effective and valuable method for the treatment of oral hemangiomas and vascular malformations.

Influence of low-dose nicotine on bone healing.

BACKGROUND Nicotine at a low concentration was suggested as a new topical drug for clinical application. It has been reported to be capable of enhancing skin wound healing. This study was designed to assess the effect of nicotine administration at a low dose on bone regeneration using a rabbit model of mandibular distraction osteogenesis. METHODS Twenty New Zealand white rabbits were randomly assigned to nicotine group and control group. A total of 0.75 g, 60-day time release, nicotine pellets or placebos were implanted in the neck subcutaneous tissue of the rabbits. The nicotine or placebo exposure time for all the animals was 7 weeks. Unilateral mandibular distraction osteogenesis was performed. Five animals in each group were killed on week 2 and week 4 of consolidation, respectively. The mandibular samples were subjected to radiographic, histologic, and immunohistochemical analysis. RESULTS Nicotine at low dose showed no significant effect on the expression of bone morphogenetic protein-2 and on the radiodensity of bone regeneration. However, the delayed bone healing was detected in the nicotine group by histologic examination. CONCLUSIONS These findings imply a potential risk of compromised bone healing in patients taking nicotine medication. Further clinical studies are necessary to assess the risk of nicotine medication on reconstructive surgery.